chr8-143567393-G-T

Variant names:

• chr8-143567393-G-T
• rs947413611
• NM_001100878.2:c.2006C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001100878.2(MROH6):​c.2006C>A​(p.Ala669Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000727 in 1,100,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A669V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 36)
  • Exomes 𝑓: 0.0000073 (0 hom.)
• Consequence: MROH6 NM_001100878.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380
• Publications: 0 publications found

Genes affected

MROH6 (HGNC:27814): (maestro heat like repeat family member 6)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11030251).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH6	NM_001100878.2	c.2006C>A	p.Ala669Glu	missense_variant	Exon 14 of 14	ENST00000398882.8	NP_001094348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MROH6	ENST00000398882.8	c.2006C>A	p.Ala669Glu	missense_variant	Exon 14 of 14	5	NM_001100878.2	ENSP00000381857.3

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome AF: 0.00000727 AC: 8 AN: 1100726 Hom.: 0 Cov.: 45 AF XY: 0.00000957 AC XY: 5 AN XY: 522674

African (AFR) AF: 0.0000435 AC: 1 AN: 22986

American (AMR) AF: 0.00 AC: 0 AN: 8612

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14614

East Asian (EAS) AF: 0.00 AC: 0 AN: 26520

South Asian (SAS) AF: 0.0000373 AC: 1 AN: 26836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22870

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2964

European-Non Finnish (NFE) AF: 0.00000645 AC: 6 AN: 930820

Other (OTH) AF: 0.00 AC: 0 AN: 44504

GnomAD4 genome Cov.: 36

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0066	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.11	N
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.38
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.079
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.025	D
Polyphen		0.12	B
Vest4		0.27
MutPred		0.21		Loss of MoRF binding (P = 0.0522);
MVP		0.030
MPC		0.042
ClinPred		0.11	T
GERP RS		0.89
Varity_R		0.11
gMVP		0.24
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs947413611; hg19: chr8-144649563;